Policy for Research Using Human Subjects or Human-Derived Materials
Abstract9.0400 Policy for Research Using Human Subjects or Human-Derived Materials: All research using human subjects or human-derived materials conducted by Georgia Health Sciences University faculty, staff, or students must obtain Institutional Review Board (IRB) approval prior to the initiation of any research activities that involves human subjects or human-derived materials.
AffiliationGeorgia Health Sciences University
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes.Merkley, Mark A.; Hildebrandt, Ellen; Podolsky, Robert H.; Arnouk, Hilal; Ferris, Daron G.; Dynan, William S.; Stöppler, Hubert; Institute of Molecular Medicine and Genetics; Center for Biotechnology and Genomic Medicine; Department of Obstetrics and Gynecology; et al. (2009-09-16)BACKGROUND: Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. RESULTS: Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19-21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27). CONCLUSION: This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.